The Journal of Experimental Medicine
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Published online 22 November 2004 doi:10.1084/jem.20040809
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 11, 1519-1524
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Brief Definitive Report

 Clonal Type I Interferon–producing and Dendritic Cell Precursors Are Contained in Both Human Lymphoid and Myeloid Progenitor Populations

Laurie Chicha1, David Jarrossay1, and Markus G. Manz1,2

1 Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland
2 Department of Medicine II, Eberhard-Karls-University Medical School, 72076 Tuebingen, Germany

Address correspondence to Markus G. Manz, Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland. Phone: 41-91-820-0311; Fax: 41-91-820-0312; email: manz{at}irb.unisi.ch

Because of different cytokine responsiveness, surface receptor, and transcription factor expression, human CD11c– natural type I interferon–producing cells (IPCs) and CD11c+ dendritic cells were thought to derive through lymphoid and myeloid hematopoietic developmental pathways, respectively. To directly test this hypothesis, we used an in vitro assay allowing simultaneous IPC, dendritic cell, and B cell development and we tested lymphoid and myeloid committed hematopoietic progenitor cells for their developmental capacity. Lymphoid and common myeloid and granulocyte/macrophage progenitors were capable of developing into both functional IPCs, expressing gene transcripts thought to be associated with lymphoid lineage development, and into dendritic cells. However, clonal progenitors for both populations were about fivefold more frequent within myeloid committed progenitor cells. Thus, in humans as in mice, natural IPC and dendritic cell development robustly segregates with myeloid differentiation. This would fit with natural interferon type I–producing cell and dendritic cell activity in innate immunity, the evolutionary older arm of the cellular immune system.

Key Words: human hematopoietic progenitors • plasmacytoid dendritic cells • dendritic cells • development • hematopoietic lineage commitment


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